This application requests 5 years of funding through the K25 Mentored Quantitative Research Scientist Development Award mechanism. With a Ph.D. degree in engineering, the candidate received additional training in experimental psychology, focusing specifically on human emotional speech processing and voice pattern recognition. As a postdoctoral associate and, more recently, a research faculty at Yale University, he conducted numerous fMRI studies on healthy individuals and patients with substance use disorders. The candidate's career goals are to build on an extensive background in engineering and computation and continue to develop advanced, novel computational methods to investigate altered cerebral function and connectivity as a circuit level biomarker of substance misuse. The support of this K25 award will provide time and resources for him to solidify his knowledge of brain structure and function and facilitate an independent career in addiction neuroscience research. His training plan will cover: 1) systems, cognitive, and addiction neuroscience through formal course work and research collaboration with his mentors; 2) neuroimaging, with a specific focus on state-of-the-art imaging techniques, experimental psychology, and design of fMRI studies; 3) biology, treatment, and clinical trials research of substance abuse; 4) scientific writing; and 5) grant preparation. To implement this training plan, the candidate has assembled an outstanding team of mentors and proposed to use a novel computational approach to understand how thalamic cortical functions are compromised and how these deficits are related to relapse in chronic cocaine users. Specifically, he proposed to employ resting state and task-modulated connectivity analysis to functionally parcellate the thalamus during resting, cognitive control, reward processing and cue-induced craving, and to investigate how thalamic cortical circuit functions are altered in individuals with cocaine dependence. With the concurrent support of an ongoing R01 study, the candidate will study more than 250 cocaine dependent patients in a longitudinal setting to identify thalamic cortical predictors of relapse. The study will thus advance our understanding of the etiological processes of cocaine addiction in multiple dimensions. The study may also facilitate research of other neuropsychiatric disorders through its new conceptual and methodological platform. By completing the proposed training and research projects, the candidate will benefit extensively from the support of this K25 award in achieving his career goal to become an independent investigator in systems and addiction neuroscience research.